The goal of this research is to develop new procedures which use carbon-carbon double bonds as activating groups for carbon-carbon bond forming reactions and to use these reactions for the synthesis of biologically active natural products. Carbon-carbon bond forming reactions are key features of both large scale industrial synthesis and complex natural product synthesis. The specific aims for the period of this proposal are two-fold. Intramoleclular [2+2] cycloadditions of ketenes to alkenes and oxidative free-radical cyclizations will be developed as new synthetic methods which use carbon-carbon double bonds as activating groups for carbon-carbon bond forming reactions. Intramolecular [2+2] cycloadditions of ketenes to alkenes will extend the scope of the cycloaddition to less reactive alkenes and ketenes and provide an efficient route to complex polycyclic compounds. The intramolecular nature of the reaction will lead to a high degree of regio- and stereoselectivity. This reaction will be used for the synthesis of an intermediate for phyllanthocin synthesis, isocomene, pentalenene, avenaciolide, prostaglandin intermediates, Prelog-Djerassi lactone and jasmonic acid. Oxidative free-radical cyclizations will be used to prepare a variety of highly functionalized cyclic and polycyclic compounds not available by other routes. Mn(OAc)3 will oxidize a 1,3-dicarbonyl compound to give a radical which adds intramolecularly to an alkene to give a radical which is oxidized to a cation. The substitution pattern of the products will be different from that available by cation-olefin cyclization. The products will be more highly functionalized than those available from normal free radical cyclization. This reaction will be used for the preparation of intermediates useful for the synthesis of aphidocolin and a variety of other diterpenoids and sedanenolide.